Elicit: Dulaglutide and Cardiovascular Outcomes in Type 2 Diabetes
Dulaglutide and Cardiovascular Outcomes in Type 2 Diabetes
Evidence for dulaglutide reducing major adverse cardiovascular events in type 2 diabetes (MACE outcomes)
Summary of Findings
Dulaglutide 1.5 mg weekly reduces major adverse cardiovascular events by 12% in type 2 diabetes patients, with particularly strong benefits for stroke reduction (24%) but no significant effect on myocardial infarction. These cardiovascular benefits extend across patients with and without established cardiovascular disease.
Abstract
Dulaglutide 1.5 mg weekly reduces major adverse cardiovascular events in type 2 diabetes by 12% compared to placebo (HR 0.88, 95% CI 0.79-0.99, p=0.026), based on the REWIND trial of 9,901 participants followed for a median of 5.4 years. This benefit was mainly driven by a 24% reduction in stroke (HR 0.76, p=0.010), particularly ischemic stroke (HR 0.75, p=0.012).
Methods
We analyzed 10 sources from an initial pool of 200, screening based on criteria including population, intervention, outcomes, study design, and more.
Papers screened out: 190 Papers included for extraction: 10
Results
The evidence base comprised 10 sources examining dulaglutide’s effects on MACE outcomes in type 2 diabetes. Most sources reported on the REWIND trial, while one compared tirzepatide to dulaglutide.
MACE Definition and Components
The primary MACE definition across studies was predominantly a 3-point composite: cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.
Effects on Primary MACE Outcomes
| Study | MACE Definition | Dulaglutide Events | Comparator Events | Hazard Ratio (95% CI) | P-value | Statistical Conclusion |
|---|---|---|---|---|---|---|
| REWIND (Konig et al., 2021) | 3-point MACE | Not reported | Not reported | 0.88 (0.79, 0.99) | 0.026 | Superiority |
| REWIND (Lipscombe, 2019) | 3-point MACE | 2.35 per 100 person-years | 2.66 per 100 person-years | RRR: 11% (1 to 20) | Not reported | Significant reduction |
Individual MACE Components
| Component | Study | Dulaglutide Events | Comparator Events | Hazard Ratio (95% CI) | P-value |
|---|---|---|---|---|---|
| Nonfatal stroke | REWIND (Lipscombe, 2019) | 0.52 per 100 person-years | 0.69 per 100 person-years | RRR: 24% (5 to 39) | Not reported |
| Ischemic stroke | REWIND (Gerstein et al., 2020) | Not reported | Not reported | 0.75 (0.59-0.94) | 0.012 |
| Nonfatal MI | REWIND (Lipscombe, 2019) | Not reported | Not reported | 0.96 (0.79 to 1.16) | Not reported |
Total Cardiovascular Burden Analysis
Total MACE outcomes in the REWIND trial showed a reduction in events, with a total of 1,972 MACE outcomes from 9,901 participants. The incidence of total MACE with dulaglutide was reduced significantly.
Subgroup Analyses
Subgroup analyses indicated consistent MACE-3 risk reduction across various diabetes complications:
- eGFR <60 mL/min/1.73m²: HR 0.93 (0.76–1.13)
- eGFR ≥60 mL/min/1.73m²: HR 0.86 (0.75–0.99)
Mechanisms of MACE Reduction
Improvements in HbA1c and albuminuria account for 65% of the cardiovascular outcomes, suggesting a combined effect of glycemic control.
Conclusion
Dulaglutide consistently reduces cardiovascular events in type 2 diabetes across various subgroups and analyses. The cardiovascular benefits especially relating to stroke outcomes indicate its potential role in primary and secondary prevention among diabetic patients.